INTERCELLULAR-ADHESION MOLECULE-1 IS AN ENDOTHELIAL-CELL ADHESION RECEPTOR FOR PLASMODIUM-FALCIPARUM
INTERCELLULAR-ADHESION MOLECULE-1 IS AN ENDOTHELIAL-CELL ADHESION RECEPTOR FOR PLASMODIUM-FALCIPARUM
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DOI：
10.1038/341057a0
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发表时间：
1989-09-07
期刊：
影响因子：
64.8
通讯作者：
MARSH, K
中科院分区：
文献类型：
--
作者：
BERENDT, AR;SIMMONS, DL;MARSH, K
恶性疟原虫感染的严重疟疾发病机制中的主要事件被认为是滋养体和疟原虫感染的红细胞粘附于毛细血管内皮1，这一过程称为隔离。识别用作受体的内皮分子是理解这种疾病过程的重要步骤。最近的工作涉及膜糖蛋白CD 36（血小板糖蛋白IV;参考文献2-5）和多功能糖蛋白血小板反应蛋白6as受体。尽管CD 36广泛分布于微血管内皮7，但它可能并不表达于发生隔离的所有毛细血管床上，尤其是在脑中8。血小板反应蛋白在体外或体内细胞粘附中的作用不太确定4，9。我们已经注意到，一些寄生虫与人脐静脉内皮细胞的结合不依赖于CD 36或血小板反应蛋白。为了筛选替代受体，我们已经开发了一种新的细胞粘附试验，使用转染COS细胞，这证实了CD 36是一种细胞粘附受体。此外，我们还发现P.恶性疟原虫与转染有编码细胞间粘附分子-1的互补DNA的COS细胞结合。由于这种分子广泛分布在毛细血管上，并且是可诱导的10，这一发现可能与严重疟疾的发病机制有关。
THE primary event in the pathogenesis of severe malaria inPlasmodium falciparuminfection is thought fo be adherence of trophozoite- and schizont-infected erythrocytes to capillary endothelium1, a process called sequestration. Identifying the endothelial molecules used as receptors is an essential step in understanding this disease process. Recent work implicates the membrane glycoprotein CD36 (platelet glycoprotein IV; refs 2–5) and the multi-functional glycoprotein thrombospondin6as receptors. Although CD36 has a widespread distribution on microvas-cular endothelium7, it may not be expressed on all capillary beds where sequestration occurs, especially in the brain8. The role of thrombospondin in cell adhesion,in vitroorin vivo, is less certain4,9. We have noticed that some parasites bind to human umbilical-vein endothelial cells independently of CD36 or thrombospondin. To screen for alternative receptors, we have developed a novel cell-adhesion assay using transfected COS cells, which confirms that CD36 is a cell-adhesion receptor. In addition, we find that an endothelial-binding line ofP. falciparumbinds to COS cells transfected with a complementary DNA encoding intercellular adhesion molecule-1. As this molecule is widely distributed on capillaries and is inducible10, this finding may be relevant to the pathogenesis of severe malaria.